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. 2020 Feb 10;17(1):6.
doi: 10.1186/s12981-020-0262-y.

HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study

Aurelio Orta-Resendiz  1 , Roberto A Rodriguez-Diaz  2 , Luis A Angulo-Medina  2 , Mario Hernandez-Flores  2 , Luis E Soto-Ramirez  3
Affiliations

HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study

Aurelio Orta-Resendiz et al. AIDS Res Ther. .

Abstract

Background: In resource-limited settings, multi-experienced HIV infected patients are often prescribed raltegravir for salvage therapy. Patients failing raltegravir-containing regimens require other drugs including other integrase inhibitors. In this context, real-life data about the resistance and cross-resistance pathways between integrase inhibitors is limited. The aim of this study was to investigate integrase resistance pathways in a cohort of Mexican multi-experienced patients failing of a raltegravir-containing salvage regimen.

Methods: Twenty-five plasma samples from subjects failing antiretroviral regimens which included raltegravir were obtained from various healthcare centres from 2009 to 2017 in Mexico. Antiretroviral history and demographics were collected. Samples were processed for integrase resistance genotyping testing by sequencing. The viral sequences were analysed with the Stanford HIV drug resistance database algorithm. Data was analysed with SPSS Statistics software.

Results: We found a mean viral load of 4.17 log10 c/mL (SD 1.11) at the time of virologic failure. Forty-eight percent of the samples were raltegravir resistant. The Y143R/H/C substitutions were the most prevalent, followed by the N155H, and both Q148H/K and G140S/A in the same proportion. The Q148 + G140 combination was found in (12%) of the samples. Cross-resistance to elvitegravir was found in 83.3% and in 18.2% for both dolutegravir and bictegravir. Thirteen samples (52%) were susceptible to the four integrase strand-transfer inhibitors.

Conclusions: Our findings suggest a high occurrence of resistance and cross-resistance to other integrase inhibitors among multi-experienced subjects failing raltegravir. We found a modestly lower proportion of cross-resistance to dolutegravir than data from clinical trials. Likely this drug could be used for salvage therapy. Explanations for the absence of mutations in half of the samples, other than reduced adherence, should be further investigated. Close surveillance is needed.

Keywords: Cross-resistance; Drug resistance; Integrase inhibitors; Multi-experienced; Raltegravir; Sequencing.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Proportion of samples with genotype-predicted resistance to integrase strand-transfer inhibitors. Absolute numbers are shown above each bar. RAL raltegravir, EVG elvitegravir, DTG dolutegravir, BIC bictegravir, S Susceptible (score 0–9), PLLR Potential low-level resistance (score 10–14), LLR Low-level resistance (score 15–29), IR Intermediate resistance (score 30–59), HLR High-level resistance (score ≥ 60); N = 25
Fig. 2
Fig. 2
Frequencies of samples with integrase resistance-associated mutations. INSTIs integrase strand transfer inhibitors, RAMs resistance associated mutations; N = 25
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References

    1. Lee FJ, Amin J, Carr A. Efficacy of initial antiretroviral therapy for HIV-1 infection in adults: a systematic review and meta-analysis of 114 studies with up to 144 weeks’ follow-up. PLoS ONE. 2014;9:e97482. doi: 10.1371/journal.pone.0097482. - DOI - PMC - PubMed
    1. Chêne G, Sterne JAC, May M, Costagliola D, Ledergerber B, Phillips AN, et al. Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies. Lancet. 2003;362:679–686. doi: 10.1016/S0140-6736(03)14229-8. - DOI - PubMed
    1. Yoshimura K. Current status of HIV/AIDS in the ART era. J Infect Chemother. 2017;23:12–16. doi: 10.1016/j.jiac.2016.10.002. - DOI - PubMed
    1. INSIGHT START Study Group. Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015 doi: 10.1056/NEJMoa1506816. - DOI - PMC - PubMed
    1. Tang MW, Shafer RW. HIV-1 antiretroviral resistance: scientific principles and clinical applications. Drugs. 2012;72:e1–e25. doi: 10.2165/11633630-000000000-00000. - DOI - PMC - PubMed

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